1. Field of the Invention
This invention relates generally to micro-fluidic biological micro-electro-mechanical systems (MEMS).
2. Description of Related Art
The use of micro-electro-mechanical systems (MEMS) in biological research is becoming increasingly common. Micro-devices allow for relatively easy observation and manipulation of individual cells, proteins, or other biological macromolecules. Sample sizes for such experiments may be reduced when using MEMS as compared to traditional techniques. J. D. Trumbull, et al., IEEE Transactions on Biomed. Eng. 47, 3 (2000). This allows biological systems to be studied at a new level of resolution while minimizing the materials required for an experiment.
Initially, microfluidic devices were used primarily for capillary electrophoresis. S. Jacobson, et al., Anal. Chem. 66 (1994) 1114; D. J. Harrison, et al., Anal. Chem. 64 (1992) 1926; Z. Liang, et al.; Anal. Chem. 68 (1996) 1040. Recently, there has been interest in incorporating a complete array of functional units, e.g., valves, pumps, reaction chambers, etc., onto a single chip to create a lab-on-a-chip (LOC). J. Voldman, et al., J. Microelectromech. Sys. 9 (2000) 295; I. Glasgow, et al., IEEE Transactions on Biomed. Eng. 48 (2001) 570; T. Fujii, Microelectronic Eng., 61-62 (2002) 907; A. Yamaguchi, et al., Analytical Chimica Acta., 468 (2002) 143; J. H. Kim, et al., Sensors and Actuators A. 95 (2002) 108; M. Krishnan, et al., Curr. Opinion Biotech. 12 (2001) 92; A. Hatch, et al., J. Microelectromech. Sys. 10 (2002) 215.
The ability to create MEMS and other devices such as biosensors and microarrays requires facile methods to precisely control surfaces. A variety of patterning techniques can be used to produce desired structures, while various methods have been investigated to control surface chemistries. For instance, microfabrication techniques are routinely applied to create patterned inorganic surfaces with nanometer to micrometer scale resolution. Xia, Y., et al., Angew. Chem, Int. Ed. Engl., 37, 550-575 (1998).
A variety of methods are presently available for fabrication of microfluidic devices. Channels can be micromachined into silicon using traditional microelectronics techniques. M. de Boer, et al., J. Microelectromech. Sys. 9, 94 (2000); G. Kovacs, et al., Proc. IEEE, 86, 1536 (1998); J. Bustillo, et al., Proc. IEEE, 86, 1552 (1998). Glass can be a substrate for biological applications, allowing for visual observation of activity inside the channel. C. H. Lin, et al. J. Micromech. Microeng., 11, 726 (2001). However, glass and silicon processing are expensive and time-consuming, and often require hazardous chemicals and expensive machinery.
Other drawbacks limit the effectiveness of conventional microfluidic devices. For example, current technology relies heavily on either manual alignment of bio-MEMS layers or complex and expensive thin film and lithographic processing techniques to ensure alignment. Current technology also relies on single-level microfluidic devices in which fluid insertion is carried out by microsyringes, exploiting capillary action and sometimes electrokinetics. In some cases, fluidic inputs and outputs have been construed by manual alignment of fluidic connections to the bioMEMS and subsequent hand-gluing of the seals. Neither of these approaches readily enables leak-tight fluidic sealing or direct integration of the inputs/outputs with the package level.